1. Field of the Invention
The present invention is directed to methods and devices for the characterization of cardiac rhythms and, particularly, characterization of ventricular fibrillation and to methods and devices to be used in the treatment of ventricular fibrillation based upon the characterization of ventricular fibrillation.
References set forth herein may facilitate understanding of the present invention or the background of the present invention. Inclusion of a reference herein is not intended to and does not constitute an admission that the reference is available as prior art with respect to the present invention.
2. Prior Art
Ventricular Fibrillation (VF) is an abnormal and chaotic heart rhythm that results in death if not terminated within a short time period, generally accepted as less than 10 to 20 minutes. If cardiopulmonary resuscitation is applied, this interval maybe extended to as much as 30 minutes on rare occasions. There are an estimated 350,000 cardiac arrests which occur each year in the United States. VF is present in approximately 40% of these non-traumatic sudden death events. See Homberg, M, et al., “Incidence, duration and survival of ventricular fibrillation in out-of-hospital cardiac arrest patients in Sweden,” Resuscitation, 44(1):7-17, 2000; and Cobb, L, et al., “Changing incidence of out-of-hospital ventricular fibrillation,” 1980-2000, JAMA, 288(23):3008-13, 2000.
Ventricular Fibrillation is terminated by the application of an electric shock. It has become clear that this shock is most successful when delivered in the first 4-5 minutes of VF. It has also become evident that in patients in whom VF has persisted for more than 4-5 minutes, if CPR is performed before defibrillation is attempted, survival increases significantly. In a study of CPR for 90 seconds prior to defibrillation, there was a demonstrated increase in survival from 17% to 27% among patients given CPR prior to defibrillation when the response times were over four minutes, see Cobb, L A, et al., “Influence of cardiopulmonary resuscitation prior to defibrillation in patients with out-of-hospital ventricular fibrillation,” JAMA, 281(13):1182-8, 1999.
In a second study, see Wik, L, et al., “Delaying defibrillation to give basic cardiopulmonary resuscitation to patients with out-of-hospital ventricular fibrillation,” JAMA, 289(11):1389-95, 2003, patients who had ambulance response times of over 5 minutes (indicating a duration of VF of 5 minutes or longer) demonstrated an increase in survival from 4% to 22% when 3 minutes of CPR was done prior to defibrillation attempts.
Since attempting defibrillation with an electric shock prior to giving CPR results in a decreased survival rate, it may be concluded that defibrillation is detrimental if given as the initial treatment in prolonged ventricular fibrillation of over 5 minutes duration. In these patients CPR should be performed first and in some cases the administration of medications and other therapies prior to defibrillation attempts may also increase survival rates.
Since it is usually impossible to objectively determine the duration of ventricular fibrillation accurately from the clinical situation (i.e. from bystanders) during the cardiac arrest event, prior art has focused on efforts to determine the duration and/or likelihood of successful defibrillation based on the examination of a short segment of the VF waveform. The duration of VF has been used as an estimator of the probability that defibrillation attempts will be successful. This is a well established marker and the probability of survival (as a result of successful defibrillation) is accepted as decreasing by approximately 10% for each minute that VF persists, see “American Heart Association in Collaboration with the International Liaison Committee on Resuscitation: Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care: An International Consensus on Science,” Circulation 2000, 102(8)(Suppl. I) I -136-I-157 and see Callans, D J, “Out-of-hospital cardiac arrest-the solution is shocking,” JAMA, 351(7):632-4, 2004.
Analysis of a short segment of ventricular fibrillation could, therefore, indicate two important features. Firstly, it could indicate the probability that an electric shock will result in the conversion of ventricular fibrillation to a perfusing, organized cardiac rhythm providing circulation to the patient. If this probability is high, such a shock should be immediately delivered. Secondly, it could indicate that the duration of ventricular fibrillation is longer than 4 or 5 minutes and/or that survival would be greatly improved if CPR, and perhaps other measures, were to be provided prior to a defibrillating shock. The prior art in this area has focused on various means to identify these two groups of patients based on the ECG waveform. Included in this reasoning is the consideration that a measure that is able to separate patients who would respond to electrical therapy from those that would not respond based on duration estimates would also be able to separate responders from non-responders even if the cause of the non-response was some other physiologic variable such as continued ischemia, metabolic derangements poisoning the myocardium, etc. In summary, a measure that is derived from studies based on duration estimates of ventricular fibrillation may also work well to estimate the overall physiology of the myocardium as it relates to probability of successful defibrillation by shock and/or probability of eventual survival.
It has been recognized for years that the roughness of the VF waveform seemed to correlate with the likelihood of successful defibrillation, however earlier efforts to quantify this observation have led to poor results. Prior efforts to quantify roughness based on amplitude have been unsuccessful because of many factors, including body habitus, electrode position, electrode conductance, myocardial mass, coexistent pulmonary disease, etc., See Weaver, W D, et al., “Amplitude of ventricular fibrillation waveform and outcome after cardiac arrest,” Ann Intern Med, 102(1):53-5 1985; and Hargarten, K M, et al., “Prehospital experience with coarse ventricular fibrillation: a ten year review,” Ann Emerg Med, 19(2):157-62 1990.
A number of subsequent attempts have focused on examining the underlying average frequency composition of the waveform as derived from Fourier analysis. See Dzwonczyk, R, et al., “The median frequency of the ECG during ventricular fibrillation: its use in an algorithm for estimating the duration of cardiac arrest,” IEEE Trans Biomed Eng, 37:640-6 1990; Brown, C G and Dzwonszyk, R, “Signal analysis of the human electrocardiogram during ventricular fibrillation: frequency and amplitude parameters as predictors of successful countershock,” Ann Emerg Med, 27(2):184-8, 1996; and Berg, R A, et al., “Precountershock cardiopulmonary resuscitation improves ventricular fibrillation median frequency and myocardial readiness for successful defibrillation from prolonged ventricular fibrillation: a randomized, controlled swine study,” Ann Emerg Med, 40(6):563-70, 2002; U.S. Pat. Nos. 5,957,856 and 6,171,257. Such methods by themselves are poor predictors of ventricular fibrillation duration primarily because the median frequency and all frequency measures are multiphasic, exhibiting an initial increase to about 4 minutes, a decline through about 10 minutes and then a rise to time periods beyond 12 minutes, see Sherman, L D et al., “Angular velocity: a new method to improve prediction of ventricular fibrillation duration,” Resuscitation, 60(1): 79-90, 2004. This makes a frequency in the middle range consistent with several different duration estimates.
Careful study of surface ECG waveforms during VF has led to the consideration that the apparently random activity may in fact be a manifestation of chaos. See, for example, Gray, R A, et al., “Spatial and temporal organization during cardiac fibrillation,” Nature, 392:758 1998; Witkowski, F X, et al., “Spatiotemporal evolution of ventricular fibrillation,” Nature, 392:78-82 1998; Witkowski, F X, et al., “Evidence for determinism in ventricular fibrillation”, Phys Rev Lett, 75(6): 1230-3, 1995; Garfinkel, A, et al., “Quasiperiodicity and chaos in cardiac fibrillation,” J Clin Invest, 99(2):305-14, 1997; and Hastings, H M, et al., “Nonlinear dynamics in ventricular fibrillation,” Proc Natl Acad Sci USA, 93:10495-9, 1996.
Using methods derived from the fields of fractal geometry and nonlinear, chaotic dynamics, several studies addressed the problem of establishing the prior duration of VF in clinical and other settings through use of the scaling exponent (ScE), see Callaway, C W, et al., “Scaling structure of electrocardiographic waveform during prolonged ventricular fibrillation in swine,” Pacing Clin Electrophysiol, 2:180-91, 2000; and Sherman, L D, et al., “Ventricular fibrillation exhibits dynamical properties and self-similarity,” Resuscitation, 47(2):163-73, 2000; and Lightfoot et al., “Dynamic nature of electrocardiographic waveform predicts rescue shock outcome in porcine ventricular fibrillation,” Ann Emerg Med, 42:230-241, 2003. The scaling exponent is a measure based on fractal geometry that measures the roughness of the VF waveform. It can be calculated in less than two seconds from a five-second surface recording of the ECG voltages. The scaling exponent has been found to increase over time from a low level of approximately 1.05 to a high level near 1.8 and provides a quantitative measure of the roughness of the VF waveform that is observed to change over time. The scaling exponent has also been shown to be predictive of the probability of successful defibrillation in patients treated with automated defibrillators see Callaway, C W, et al., “Scaling exponent predicts defibrillation success for out-of-hospital ventricular fibrillation cardiac arrest,” Circulation, 103(12):1656-61, 2001; and U.S. Pat. No. 6,438,419, the disclosures of which are incorporated herein by reference. Recently, the scaling exponent was used to evaluate the effect of performing initial immediate defibrillating shock versus starting resuscitation with CPR and/or medication prior to countershock, see Menegazzi, J J, et al., “Ventricular Fibrillation scaling exponent can guide timing of defibrillation and other therapies,” Circulation, 109(7):926-931, 2004. Those studies have demonstrated that in prolonged VF (that is, ventricular fibrillation in which the ScE has progressed to 1.3 or higher), providing CPR and drugs significantly increases survival. The converse of that observation is that defibrillating prior to other interventions in prolonged VF is detrimental and leads to a decrease in potential survival.
The scaling exponent has a rise in value over the first 5 minutes and then plateaus for a period of 4 minutes before again rising. This makes separation of time periods before and after 5 minutes difficult. A method based on non-liner dynamic methods which provides a measure related to the frequency of the ventricular fibrillation waveform was therefore developed which is termed the “angular velocity” (AV), see Sherman, L D, et al., “Angular velocity: a new method to improve prediction of ventricular fibrillation duration”, Resuscitation, 60(1): 79-90, 2004. The angular velocity, (AV), is based on the formation (from 3 ‘lagged’ copies of the time series data of the VF waveform) of a structure in three dimensional phase space which rotates around a central point in a disc shaped region. The velocity of rotation of the leading edge of the position vector which forms this structure over time decreases with the duration of VF. If a 5 second recording of VF is examined with this method, it provides an estimate of the time period at which the VF was obtained.
Although each of the two methods, the scaling exponent and the angular velocity, have limitations individually, they can be combined to increase the sensitivity and specificity of the overall analysis of ventricular fibrillation into episodes less than 5 minutes and episodes greater than 5 minutes. In fact, the combination of these two methods in the laboratory with VF recorded at 1000 samples/sec and without filtering of the signal allows one to predict with 90% sensitivity that the VF being examined is from a subject with VF of less than 5 minutes duration. Specificity with this method is 75%.
The scaling exponent was developed in a laboratory setting in which recording could be done in an optimal manner in order to acquire data sufficient to calculate the scaling exponent and the angular velocity accurately. Specifically, the recording rates were 1000 samples/second and the data were acquired without filtering of any type. Modern cardiac defibrillators, AEDs, and monitoring equipment that is currently in use do not provide for data acquisition at these rates and the signal acquired is highly filtered, usually below 40 hertz, in order to apply computer algorithms which are used to analyze the ECG traces for cardiac rhythm, rate and other features of interest. Typical sampling rates are less than 125 samples per second and the signal is low pass filtered to allow only the part of the signal less than 40 hertz to be acquired. This is not a problem for frequency based measures, such as Fourier analysis or for angular velocity measurements, because the power of frequencies present in ventricular fibrillation are predominantly below 20 hertz. However, studies of filtering and sampling rates do demonstrate that the value of the scaling exponent is severely decreased by filtering and by reducing the sampling rate. This is demonstrated in FIGS. 1 and 2 which show the mean ScE calculated over a period of 13 minutes from VF recorded at 1000 samples/sec without filtering in FIG. 1 and the ScE for the same group of recordings decimated to a rate of 62.5 samples/sec and low pass filtered to below 31.25 hz. In these real world circumstances, the scaling exponent loses almost all of its predictive ability. In contrast, the angular velocity is not severely affected by the recording conditions as present in currently used devices. This is shown in FIG. 6. In order to be able to separate VF of under five minutes from that over 5 minutes and to better predict duration of VF and the probability of successful defibrillation attempts, a method which measures information which is similar to that measured by the scaling exponent but which is not affected by the sampling rates and digital filters present in currently used clinical devices is clearly needed.
While progress has been made in developing methods for determining the duration of ventricular fibrillation and likelihood of successful defibrillation, it remains desirable to develop improved devices and methods for determining the duration of ventricular fibrillation as well as improved treatment devices, methods and protocols for treatment of ventricular fibrillation based on these.